The role
that sunlight-derived vitamin D has in modulating lung health, particularly in
allergic and asthmatic individuals has recently come under intense scrutiny.
Our studies have shown that ultraviolet radiation (UVR)
suppresses the development of allergic airway disease, the murine model of
asthma. There are also latitude gradients for asthma incidence, with greater
prevalence for increasing distance from the equator, confirming the potential
importance of UVR and UVR-induced mediators like vitamin D in modulating
allergic lung disease. Indeed, vitamin D synthesized after UV exposure of the
skin may directly suppress allergic disease. Using physiologically-relevant
murine models we have scrutinized how vitamin D deficiency or UVR-induced
vitamin D modulate the development of allergic airway disease, using the
experimental allergen ovalbumin, and T-helper type-2 skewing adjuvant,
aluminium hydroxide (alum). The effects of ‘lifetime’ vitamin D deficiency were
first examined in BALB/c mice that were maintained on either a vitamin D3-containing
or -null diet from conception until adulthood. Vitamin D-replete and -deficient
mice had mean serum levels of 25-hydroxyvitamin D (25(OH)D) that were >50
and <20 nmol.L-1, respectively. Enhanced lung inflammation was
observed in male but not female vitamin D-deficient mice following
intraperitoneal sensitization and boost with OVA (1 µg) and alum (0.2 mg) and subsequent
respiratory challenge with OVA. This inflammation was linked with increased
bacterial loads in the lungs, and both lung inflammation and bacterial levels
were inhibited by subsequent supplementation with dietary vitamin D3.
In further studies, following either acute erythemal UVR, or chronic
sub-erythemal UVR treatment, serum 25(OH)D levels significantly increased in
vitamin D3-deficient female but not male mice. To determine if
UVR-induced vitamin D was responsible for suppressing allergic airway disease,
responses were measured in mice that were able (female) or unable (male) to
synthesize vitamin D after UVR. A single dose of erythemal UVR (8 kJ/m2)
suppressed the induction of lung inflammation to a similar degree in female and
male mice. These results suggest
that UVR-induced vitamin D does not significantly contribute towards systemic
immunosuppression caused by acute erythemal UVR in mice, and highlight the
importance of other UVR-immune mediators for modulating the development of
allergic diseases like asthma.